Acute lymphoblastic leukemia (ALL) is the most common form of malignancy in children under 15 years of age, with an annual incidence rate of 37.8 per million in the United States. Childhood ALL has been demonstrated to include a heterogenous group of leukemias which markedly differ clinically and/or biologically. The Childrens Cancer Study Group (CCSG), a cooperative clinical trials study group, proposes to study the role of risk factors for childhood ALL within biologically defined subgroups. This study will assess whether biologically or clinically distinct subgroups of ALL are also etiologically distinct. The proposed study will include a total of 2000 newly diagnosed cases of childhood ALL ascertained during a four year period. Cases will be compared to a series of age-, sex- and race-matched regional population controls selected using a random digit dialing methodology. Parents of cases and controls will be interviewed by telephone. The matched pairs design will be used to quantify, within biologically distinct subgroups of ALL, the risk associated with selected environmental and genetic risk factors, as well as their possible interaction. These patient subgroups will be defined based on FAB morphology, state-of-the-art assessment of immunophenotypes and cytogenetics which will be available from CCSG for the case population. A study of this size will have sufficient power to allow identification of risk factors of even the less common ALL subtypes, in addition to providing sufficient power to allow a comprehensive assessment of specific risk factors and their interaction for childhood ALL as a whole.